There is considerable recent interest in potential relationships between exposure to stressors and the functioning of the immune system. This is because alterations in immune function might mediate the impact of stressors on the development of diseases ranging from AIDS to cancer. The proposed research has 3 general goals. 1) Most studies in the literature have used a single set of stressor parameters and measured a single aspect of immunity. Thus the immune changes which occur have not been well characterized. This has led to great difficulty in assessing the reliability and nature of immunologic change produced by stressors, and also makes it difficult to conduct research that goes beyond demonstration and explores mechanism. It is not currently possible to even ascertain what measures of immune function might be most sensitive to stress-induced change. Thus a major goal is to determine the pattern of in vivo and in vitro changes in immune function that are produced by a variety of systematically varied stressor conditions. 2) There has been very little effort directed towards determining behavioral factors which might modulate the impact of stressors on immunity and determine whether effects do or do not occur. Here 3 factors which have proven to be important in modulating other stressor effects will be studied. These are the degree of behavioral control which the organism has over the stressor, defeat, and dominance. Moreover, the relationship between these will be studied as well as the role of fear/anxiety in mediating the effects obtained. 3) The neural and neuroendocrine mechanisms which mediate the effects obtained in 1) and 2) will begin to be explored. The focus will be on changes in hypothalamic norepinephrine and pituitary-adrenal function as mediators of in vivo changes in specific antibody formation produced by stressors.